Autoimmune Diseases of Digestive Organs—A Multidisciplinary Challenge: A Focus on Hepatopancreatobiliary Manifestation

It is well known that some pathological conditions, especially of autoimmune etiology, are associated with the HLA (human leukocyte antigen) phenotype. Among these diseases, we include celiac disease, inflammatory bowel disease, autoimmune enteropathy, autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cholangitis. Immunoglobulin G4-related diseases (IgG4-related diseases) constitute a second group of autoimmune gastrointestinal, hepatobiliary and pancreatic illnesses. IgG4-related diseases are systemic and rare autoimmune illnesses. They often are connected with chronic inflammation and fibrotic reaction that can occur in any organ of the body. The most typical feature of these diseases is a mononuclear infiltrate with IgG4-positive plasma cells and self-sustaining inflammatory response. In this review, we focus especially upon the hepatopancreatobiliary system, autoimmune pancreatitis and IgG4-related sclerosing cholangitis. The cooperation of the gastroenterologist, radiologist, surgeon and histopathologist is crucial for establishing correct diagnoses and appropriate treatment, especially in IgG4 hepatopancreatobiliary diseases.

Inflammatory microRNAs in gastric mucosa are modulated by Helicobacter pylori infection and proton-pump inhibitors but not by aspirin or NSAIDs

Gastric carcinogenesis is associated with alterations of microRNAs (miRNAs) and reversal of these alterations may be a crucial element in cancer prevention. Here we evaluate the influence of H. pylori eradication, low-dose aspirin (LDA), non-steroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPI) on modification of inflammatory mucosal miRNAs miR-155 and miR-223 in Helicobacter pylori-infected and non-infected subjects. The study was performed in two parts: 1) interventional study in 20 healthy subjects with and without H. pylori infection or following eradication (each n = 10) where LDA (100 mg) was given daily for 7 days; 2) prospective case-control observational study (n = 188). MiR-155 and miR-223 expression was strongly linked to H. pylori-infection and in short-term view showed a trend for reversal after eradication. Daily LDA as well as regular NSAIDs showed no influence on miRNAs expression both in healthy subjects and patients, while regular PPI intake was associated with lower miR-155 expression in antrum of patients with chronic gastritis independent of density of neutrophils and mononuclear infiltrate. In summary, PPI but not LDA or NSAIDs were associated with modification of inflammatory miRNAs miR-155 and miR-223 in an H. pylori dependent manner. The functional role of inflammatory miR-155 and miR-223 in understanding of H. pylori-related diseases needs further evaluation.

Expression of CD44 in previously grafted alveolar bone.

Objetive: To determine the expressions of the bone surface marker CD44 in samples of alveolar bone previously regenerated with allograft, xenograft, and mixed, using the technique of guided bone regeneration. Material and Methods: This exploratory study was approved by the institutional research and ethics committee. By means of intentional sampling and after obtaining informed consent for tissue donation, 20 samples of alveolar bone previously regenerated with guided bone regeneration therapy with particulate bone graft and membrane were taken during implant placement. The samples were stained with hematoxylin-eosin for histological analysis, and by immunohistochemistry for the detection of CD44. Results: Sections with hematoxylin-eosin showed bone tissue with the presence of osteoid matrix and mature bone matrix of usual appearance. Of the CD44+ samples, 80% were allograft and 20% xenograft. The samples with allograft-xenograft were negative. There were no differences in the intensity of CD44 expression between the positive samples. The marker was expressed in osteocytes, stromal cells, mononuclear infiltrate, and some histiocytes. Eighty percent of the CD44+ samples and 100% of the samples in which 60 or more cells were labelled corresponded to allografts (p=0.000). A total of 67% of the samples from the anterior sector, and 40% from the posterior sector were CD44+ (p=0.689). Conclusion: This study shows for the first time that guided bone regeneration using allografts is more efficient for the generation of mature bone determined by the expression of CD44, compared to the use of xenografts and mixed allograft-xenograft, regardless of the regenerated anatomical area.

Pathological changes in natural infection of pheasants with highly pathogenic avian influenza A (H5N8) in Bulgaria

Introduction The study of histopathological changes caused by influenza A (H5N8) viral infection in bird species is essential for the understanding of their role in the spread of this highly infectious virus. However, there are few such studies under natural conditions in minor gallinaceous species. This article describes the pathomorphological findings in Colchis pheasants infected naturally with H5N8 during an epizootic outbreak in Bulgaria. Material and Methods Samples of internal organs of 10 carcasses were collected for histopathological and immunohistochemical evaluation, virus isolation and identification, and nucleic acid detection. Results Consistent macroscopic findings were lesions affecting the intestine, heart, lung, and pancreas. Congestion and mononuclear infiltrate were common findings in the small intestine, as were necrosis and lymphoid clusters in the lamina propria of the caeca. Congestion with small focal necrosis and gliosis with multifocal nonpurulent encephalitis were observed in the brain. Myocardial interstitial oedema and degenerative necrobiotic processes were also detected. Immunohistological analysis confirmed systemic infection and revealed influenza virus nucleoprotein in all analysed organs. Conclusion Variable necrosis was observed in the brain, liver, trachea, heart, small intestine, and caeca. Viral antigen was commonly found in the brain, heart, lung and trachea. Contact with migrating waterfowls was suspected as a reason for the outbreak.

Erdheim-Chester disease with multisystemic involvement: a diagnostic challenge

Erdheim–Chester disease (ECD) is a rare, non-inherited, non- Langerhans form of histiocytosis of unknown origin, first described in 1930. This entity is defined by a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positively for CD68. Individuals affected by this disease are typically adults between their 4th and 6th decades of life. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. Bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(−) histiocytes are identified within a biopsy specimen with aid of clinical and radiological data. Here we present a rare case of Erdheim-Chester disease in a 46 year male patient based on clinical data, radiological data, histopathological and immunohistochemistry findings.

ASHY DERMATOSIS - A CASE REPORT FROM PALMAS - TO

INTRODUCTION: Ashy dermatosis is a rare dermatosis of unknown etiology and pathogenesis, more common in people with darker skin. However, in this case report, the patient is white. CASE REPORT: A 54-year-old white woman with a history of asymptomatic gray-stained macules located on the craniocaudal axis. Despite a positive antinuclear antibody (ANA) test, the use of Plaquinol was suspended due to the fact that the patient did not present rheumatologic affections. A biopsy compatible with the condition of ashy dermatosis and post-inflammation pigmentation was performed. However, the anatomopathological examination revealed superficial perivascular dermatitis with pigmented incontinence and skin fragments, a discreet superficial perivascular inflammatory mononuclear infiltrate and mild pigmentary incontinence, confirming the clinical hypothesis of ashy dermatosis. A skin lightening lotion (Arbutin 4%, Chromabright 0.5%, Alfabisabol 1%, Nicotinamide 4%, Kojico Acid 3%, Nonionic Cream) was used for 30 days with satisfactory results, along with the substitution of antihypertensive medication. FINAL CONSIDERATIONS: The report is relevant because it is necessary to know this pathology for differential diagnosis of pigmented dermatosis and so that the best treatment can be prescribed. Keywords: Ashy Dermatosis; Hyperpigmentation; Erythema Dyschromicum Perstans. RESUMO INTRODUÇÃO: A dermatose cinzenta é uma dermatose rara, de etiologia e patogenia desconhecida, mais comum em pessoas de pele mais escura, porém no caso relatado a paciente é branca. RELATO DE CASO: Mulher de 54 anos de idade, branca, com história de máculas de coloração acinzentada, assintomáticas, localizadas no eixo craniocaudal. Apesar do FAN positivo, o uso de Plaquinol foi suspenso pela paciente não apresentar afecção reumatológica. Foi realizada uma biópsia compatível com o quadro de dermatose cinzenta bem como pigmentação pós-inflamação. No entanto, no exame anatomopatológico foi encontrada dermatite perivascular superficial com incontinência pigmentar e em fragmentos de pele, um discreto infiltrado inflamatório mononuclear perivascular superficial e leve incontinência pigmentar, confirmando a hipótese clínica de dermatose cinzenta. Uma loção clareadora (Arbutin 4%, Chromabright 0,5%, Alfabisabol 1%, Nicotinamida 4%, Ácido Kojico 3%, Creme não iônico) foi utilizada por 30 dias apresentando resultados satisfatórios, além da substituição do anti-hipertensivo. CONSIDERAÇÕES FINAIS: O relato é relevante pois deve-se conhecer essa patologia para diagnose diferencial das dermatoses pigmentadas e desta forma optar pela melhor conduta terapêutica. Palavras-chave: Dermatose cinzenta; Hiperpigmentação; Eritema Discrômico Persistente.

Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients

ObjectiveTo report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies.MethodsFrom January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients’ serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAPδ proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections.ResultsSerum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells.ConclusionsGFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.

Thinking out of theGut: a case of obscure lower GI bleeding

Clinical presentationA middle-aged man was admitted for episodes of fresh per-rectal bleeding, which were not associated with defecation. He was recently investigated for macrocytic anaemia in the outpatient haematology clinic. Examination of the perineum revealed grade 1 internal haemorrhoids with no signs of bleeding.Initial laboratory tests revealed macrocytic anaemia (haemoglobin 10.5 g/dL, normal 12.9–17.0 g/dL; mean corpuscular haemoglobin 95.3 fL, normal 80.0–95.0 fL). Peripheral blood film showing blasts, dysplastic neutrophils, nucleated red blood cells and hypogranular platelets.The patient underwent a sigmoidoscopy and rubber band ligation of the internal haemorrhoids after persistent fresh per-rectal bleeding. The bleeding persisted with the development of hypotension and a significant drop of haemoglobin to 4.8 g/dL requiring blood transfusions and intensive care monitoring. Repeated endoscopy, including intubation of the terminal ileum, revealed uncomplicated right-sided diverticulosis. CT mesenteric angiography performed during an episode of significant bleeding revealed extravasation of contrast in the ileum, but mesenteric angiography was unsuccessful, possibly due to a temporary cessation of bleeding. Bleeding subsequently recurred and in light of the persistent bleeding with no clear source and with a total of 12 units of packed cell transfused, exploratory laparotomy, on-table enteroscopy (figure 1) with small bowel resection was performed. Histopathological examination of the specimen was performed (figures 2–4).Figure 1Multiple ileal lesions with stigmata of recent bleed.Figure 2Area of ulceration associated with atypical mononuclear infiltrate.Figure 3Atypical mononuclear infiltrate composed of cells with enlarged, irregular nuclei containing variably prominent nucleoli.Figure 4Atypical cells displayed cytoplasmic expression of myeloperoxidase.QuestionWhat is the diagnosis?

Skin Findings in a Patient with Sjogren’s Syndrome

Hypergammaglobulinemic purpura (HGP) is a syndrome constellating recurrent purpura, hypergammaglobulinemia, positive rheumatoid factor (RF), anti-Ro/La antibodies, and elevated erythrocyte sedimentation rate (ESR). We present a case of a 29-year-old female who was diagnosed with Sjogren’s syndrome four years prior to presenting with rash on her lower extremities for a period of 6 months. Skin biopsy at the initial visit was consistent with leukocytoclastic vasculitis and was initiated on treatment for it. Her rash evolved into 2–5 mm scattered purpurae while she was on the treatment and a repeat biopsy showed extravasation of RBCs, a sparse mononuclear infiltrate with deposition of plasma cells, and no evidence of leukocytoclastic vasculitis, thus showing a transition from neutrophilic to mononuclear inflammatory vascular disease which is a rare occurrence. Hypergammaglobulinemic purpura sometimes turns out to be a challenging disease to manage and requires an integrated effort from the primary care doctors, rheumatologist, and dermatologist.

Clinicopathologic Correlation of Oral Lichen Planus and Oral Lichenoid Lesions: A Preliminary Study

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are clinically and histologically similar lesions but their treatment planning and prognosis are different. The review of the literature indicates numerous criteria to distinguish these two lesions; however there is a lot of inconsistency. Thus, the aim of this study was to determine the correlation of histopathology and clinical OLP and OLL diagnosis and to clarify which histopathologic criteria could best distinguish these two diagnoses. A retrospective study showed that clinically diagnosed 92 OLPs and 14 OLLs have been confirmed histopathologically in 52.2% and 42.9% of cases, respectively. In addition, histopathology showed statistically significant more eosinophils (P<0.0005), plasma cells (P<0.0005), and granulocytes (P<0.05) in OLL than OLP. To establish histopathological diagnosis of OLP and OLL it should be mandatory to define the type of cells in mononuclear infiltrate, which can be associated more accurately with clinical feature and patient history. Therefore, currently accepted diagnostic criteria for OLP and OLL should be modified and validated on a larger number of patients taking into account particular distinguishing histopathological features.